six-membered heterocyclic nitrogen...
TRANSCRIPT
SIX-MEMBERED HETEROCYCLIC NITROGEN COMPOUNDS
WITH THREE CONDENSED RINGS
C. F. H. ALLEN E'aJtman Ko&k C a m p y , Rocbesier, N. Y .
In collaboration with
G.M. BADGER, BRUCE GRAHAM, G. A. REYNOLDS, JAMES H. RICHMOND, J O H N R.THIRTLE,
J. A.VAN ALLAK, and C.V. WILSON
1958
INTERSCIENCE PUBLISHERS, INC., NEW YORK
INTERSCIENCE PUBLISHERS LTD., LON D O N
This Page Intentionally Left Blank
SIX-MEMBERED HETEROCYCLIC NITROGEN COMPOUNDS
WITH THREE CONDENSED RINGS
C. F. H. ALLEN E'aJtman Ko&k C a m p y , Rocbesier, N. Y .
In collaboration with
G.M. BADGER, BRUCE GRAHAM, G. A. REYNOLDS, JAMES H. RICHMOND, J O H N R.THIRTLE,
J. A.VAN ALLAK, and C.V. WILSON
1958
INTERSCIENCE PUBLISHERS, INC., NEW YORK
INTERSCIENCE PUBLISHERS LTD., LON D O N
SIX-MEMBERED HETEROCYCLIC
NITROGEN COMPOUNDS
WITH THREE C O N D E N S E D R I N G S
Tbis is the tweyth volume published in the series
T H E CHEMISTRY OF HETEROCYCLIC C O M P O U N D S
~~
THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS A SERIES OF MONOGRAPHS
A R N 0 LD WE IS S B E RG ER, Consulting Editor
ALL RIGHTS RESERVED. Library of Congress Catalog Card Number 45-8533.
INTERSCIENCE PUBLISHERS, INC., 250 Fifth Avenue, New York 1, N.Y.
Fov Great Britain and Novthevn I re land:
I nterscience Publishers Ltd., 88/90 Chancery Lane, London, W. C. 2
The Chemistry of Heterocyclic Compounds
The chemistry of heterocyclic compounds is one of the most complex branches of organic chemistry. I t is equally interesting for its theorctical implications, for the diversity of its synthetic procedures, and for the physio- logical and industrial significance of heterocyclic compounds.
A field of such importance and intrinsic difficulty should be made a s readily accessible as possible, and the lack of a modern detailed and com- prehensive presentation of heterocyclic chemistry is therefore keenly felt. I t is the intention of the present series to fill this gap by expert presentations of the various branches of heterocyclic chemistry. The subdivisions have been designed to cover the field in its entirety by monographs which reflect the importance and the interrelations of the various compounds, and ac- commodate the specific interests of the authors.
Resenrclz Laboratories Enstman Kodak Com@any Rochester, New York
ARNOLD WEISSBERGER
V
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The polynuclear heterocyclic compounds containing nitrogen and three fused six-membered rings are of great theoretical interest and of considerable practical importance to the drug industry. Applications to dyes and in an- alytical chemistry have been of only minor significance. It is hoped that the arrangement and the discussion of the various classes included in this volume will emphasize their similarities and significant differences. The literature has been covered through 1952.
Many students have acquired a distaste for heterocyclic chemistry, owing to “the presentation of an apparently endless series of syntheses of compounds having illogical names and systems of numbering, little mention being made of their properties.”’ In this volume the aim has been to simplify naming and numbering by use of the “a” system of nomenclature, and in an introductory chapter to collect the syntheses as far as possible by “name reactions,” pointing out the similarities and nature of the products that result from different conditions of cyclization ; a discussion of mechanisms to account for the latter is included.
The “a” system of nomenclature, which “is quite rightly preferred,’I2 has been used in this as in our earlier volume. All individual chemical sub- stances are also named according to Chemical Abstracts, and the index in- cludes all names. There have been too many inconsistencies in the past ; for instance, acridine has been numbered like anthracene, but phenanthridine has not been numbered in conformity with phenanthrene (which, however, is an unfortunate exception to the rule for hydrocarbons). In this volume all the azaphenanthrenes are numbered and oriented as in The Ring Index. Phenanthridine is 5-azaphenanthrene; it is of interest to note that the latter is also the name used in the Dyson system. A complete description of the nomenclature is given in the individual chapters.
The first part of this volume was set up with the 0x0 radical placed
close to the ring 0 instead of with the author’s double bond 0. Since the former may cause confusion with a heterocyclic oxygen, the more common double-bonded designation is preferred and used in the remainder of the book.
A series of tables listing all of the compounds reported which belong to
-. I(
C.M. Atlunson, J . Chem. SOL, 19.53, 720.
VII
* S. Coffey, J . SOC. DyersColourisfs, 68,214 (1952).
VIII Preface
the particular ring system under discussion are included in each chapter. Depending upon the numbers involved, the compounds are generally classi- fied in tables or the tables arranged in the following order, with the sub- stituent lowest on the list determining the location of a compound; for example, a substance containing both carboxyl and animo groups will be found only among the carboxyl derivatives.
1. Alkyl and Aryl Derivatives. 2. Reduction Products. 3. Halogen Derivatives. 4. Nitro Derivatives. 5. Sulfo Derivatives. 6. Amino Derivatives. 7. Hydroxy Derivatives. 8. Carboxy and Carbonyl Derivatives. 9. Miscellaneous.
Exceptions and additional tables occasionally are found primarily for the convenience of the reader.
The chapter on the relation between structure and ultraviolet ab- sorption rounds out the picture of heterocyclic systems, especially since it includes other polynuclear systems than those referred to in the title of this volume.
The authors are very grateful to Dr. D. M. Burness, Mrs. Florence Otter, and Mrs. Esther Weaver for typing, proofreading, and general editorial assistance.
Eastman Kodak Company Rochester, New York April, 195%
C . F. H. ALLEN
Authors of This Volume
C. P. H. Allen, Research Laboratories, Eastman Kodak Company, Rochester,
G. M. Badger, Department of Organic Chemistry, The University of Adelaide,
Bruce Graham, Biological Sciences Department, Stanford Research Institute,
G. A. Reynolds, Research Laboratories, Eastman Kodak Company, Rochester,
James H. Richmond, Research Laboratories, Eastman Kodak Company,
John R. Thirtle, Research Laboratories, Eastman Kodak Company, Rochester,
J. A. Van Allan, Research Laboratories, Eastman Kodak Company, Rochester,
C. V. Wilson, Research Laboratories, Eastman Kodak Company, Rochester,
New York
Adelaide, South Australia
Menlo Park, California
New York
Rochester, New York (deceased)
New York
New York
New York
IX
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Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VII
Introduction . By C . V . Wilson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Mechanism of Ring Closure . By G . A . Reynolds .................... 7
I . Azaanthracenes . By C . V . Wilson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 1 . Monoazaanthracenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
A . I-Azaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 (1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 (2) Synthesis of 1-Azaanthracene . . . . . . . . . . . . . . . . . . . . . . . . 16
(a) From 6-Aminotetralin . . . . . . . . . . . . . . . . . . . 16
(c) From 9-Chloro-I-azaanthrac . . . . . . . . . . . . . . . 17
(e) From 2.4Dicarbox y- 1-azaanthracene . . . . . . . . . . . . . . 17 Proof of Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
(3) Substituted I-Azaanthracenes . . . . . . . . . . . . . . . . . . . . . . . . 18
(b) From I-Azaanthraquinone . . . . . . . . . . . 16
(d) From 0-Xylyl Chloride and Pyridine . . . .
(a) By Ring Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Combes Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Doebner-Miller Synthesis . . . . . . . . . . . . . . . . . . . . . . . . 25
Knorr Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Miscellaneous Syntheses ........................ 30
( 1 } Alkylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 (2) Halogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 (3) Nitration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 (4) Sulfonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
C1+ NH, or NR, . . . . . . . . . . . . . . . . . . . . . . . . 36 NO, + NH, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2-CH, + 2-CH=CHR . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Skraup Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Conrad-Limpach Synthesis ...................... 26
Pfitzinger Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . 28
31 (b) By Direct Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(c) By Replacement or Alteration of Other Groups . . . . . . 35 OH+ C1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
C1-t OCH, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2-CHzCHR -+ 2-COOH .......................... 38 COOH+ H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 C1+ H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 C1-t CN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
(4) Properties of the 1-Azaanthracenes .................... 39 (a) Physical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
XI
XI1 Contents
(b) Chemical Properties .............................. (1) Salt Formation .............................. (2) Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . tion . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . (a) Photooxides and Photooxidation . . . . . . . . . . . . . . . . . . (b) Photodimerization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(6) I-hzaanthraquinone and Its Derivatives . . . . . . . . . . . . . . (a) By Ring Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) By Oxidation of 1-Azaanthracene Derivatives . . . . . . . . (c) By Direct Substitution in 1-Azaanthraquinone or Its
(5) Photochemistry of the I-Azaanthracenes
Derivatives . . . . . . . . . . (1) Halogenation . . . . . . (2) Nitration . . . . . . . . . . (3) Sulfonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(d) By Replacement or Alteration of Other Groups . . . . . . (1) Halogen Derivatives .......................... (2) Hydroxy and Methoxy Derivatives . . . . . . . . . . . . . . (3) Amino Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(e) Phomazarin ...................... . . . . . . . . . . B . 2-Azaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Syntheses of 2-Azaanthracenes ........................
(a) 2-Azaanthracene ................................ (b) 7-Methyl-2-azaanthracene ........................ (c) I-Benzyl-2-azaanthracene ........................
(3) Syntheses of 2-Azaanthraquinones .................... (a) 2-Azaanthraquinone ............................ (b) 5,8-Dihydroxy- 2-azaanthraquinone . . . . . . . . . . . . . . . .
(4) Properties of 2-Azaanthracenes ........................ 2 . Diazaanthracenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A . 1.2-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2)Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
B . 1.3-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( I ) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) By Cyclization Procedures ........................ (b) By Replacement of Other Groups . . . . . . . . . . . . . . . . . .
(3) 1,3-Diazaanthraquinones .............................. C . 1.4-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
D . 1, 5-Diazaanthracene ....................................
(2) Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) 1, 5-Diazaanthracene .............................. (b) 1 O-Methyl- 1, 5-diazaanthracene .................... (c) 2.6-Dimethyl-I, 5-diazaanthracene . . . . . . . . . . . . . . . . . .
(d) 9,lO-Diphenyl- 2-azaanthracene ....................
(2) Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Nomenclature . . . . . . . . . ..........................
40 40 40 40 41 42 42 43 43 43 45
47 47 47 48 51 51 51 53 54 55 55 56 56 57 58 58 58 58 59 59 72 73 73 73 74 75 75 75 78 79 79 79 80 81 81 81 81 82 82
(d) 2.6.Dipheny 1. 1. 5.diazaanthracene . . . . . . . . . . . . . . . . . . 85
Contents XI11
E . 1. 8.Diazaanthracene .................................... 85 (1) Nomenclature ...................................... 85 (2) Syntheses .......................................... 85
F . 1. 9-Diazaanthracene .................................... 91 (1) Nomenclature ...................................... 91 ( 2 ) Historical .......................................... 91
G . 1.1 0-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 (1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
H . 2. 3-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 ( 1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 (2) Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
I . 2. 6-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 J . 2. 9-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 K . 2.1 0-Diazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
(3) Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
(2) Syntheses . . . . . . . . . . . . . . . . . . . . . 98
(1) Nomenclature . . . . . . . . . . . . . . . . . . (2) Syntheses . . . . . . . . . . . . . . . . . . . . . . . . .
3 . Triazaanthracenes . . .............................. 118 Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 A . 1.2. 3-Triazaanthrac B . 1.2. 4-Triazaanthrac C . 1.3. 9-Triazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 D . 1.8. 9-Triazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 E . 1.9.1 0-Triazaanthracene F . 2.3. 9-Triazaanthracene . . . . . . . . . . . . . . . . . . . . . . G . 2.9.1 0-Triazaanthracene . . . . . . . . . 125
4 . Tetrazaanthracenes . . . . . . Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 A . I .2.7. 8-Tetrazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 B . 1.3.5. 7-Tetrazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 C . 1.3.6. 8-Tetrazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 D . 1.4.5. 8-Tetrazaanthraccne E . 1.4.9,lO-Tetrazaanthracene F . 2.3.6. 7-Tetrazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 G . 2.7.9.1 0-Tetrazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
5 . Pentazaanthracenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 A . 1.3.8.9.1 0-Pentazaanthraccne . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
(1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 ( 2 ) Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
6 . Hexazaanthracenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 A . 1.3.6. 8 9.1 0-Hexazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
(1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 ( 2 ) Synthesis and Proof of Structure
(2) Synthesis and Pro . . . . . . . . . . . . . . . . . . . . . . 157
. . . . . . B . 1,3,5,7,9.1O-Hexazaan
( 1 ) Nomenclature . .
C . 1.2.4.5.7. 8-Hexazaanthracene . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
II . Azaphenanthrenes . By John R . ThirtZe .......................... 165 1 . Monoazaphenanthrenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
XIV Contents
A . 1-Azaphenanthrene .................................... (1) Introduction ........................................
(3) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) From Glycerol (Skraup) .......................... (b) From a-0x0 Acids (Doebner) ...................... (c) From a$-Unsaturated Aldehydes (Doebner-Miller) . . (d) From /%Diketones (Combes) . . . . . . . . . . . . . . . . . . . . . . (e) From Acetoacetnaphthylide (Knorr) . . . . . . . . . . . . . . . . ( f ) From Ethyl a-(2-Naphthy1amino)crotonate (Conrad-
Limpach) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (9) Miscellaneous Methods ..........................
(1) Pfitzinger Reaction .......................... (2) From N-Formyl-1-naphthylamine . . . . . . . . . . . . (3) From Epichlorohydrin ...................... (4) From Ethyl Malonate ........................ (5) From I-Nitronaphthalene .................... (6) From N-1-Naphthylbenzimidyl Chloride . . . . . . . . (7) From Acetylene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (8) From 1. 3-Glycerol Dichlorohydrin . . . . . . . . . . . . . . (9) From p-Oxoaldehydes ........................
(10) From Diketone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( 1 1) From Ethyl Ethoxymethylenemalonate . . . . . . . . (12) From Ethyl Ethoxylylacetate . . . . . . . . . . . . . . . . ( 13) From N - ( 3-Chloro-2-butenyl)-I-naphthylamine . . ( 14) From 1-Tetralone and Ally1 Cyanide
(2) Nomenclature ......................................
(4) Substitution Reactions . . . (a) Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . .
B . 2-Azaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( 1 ) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Reactions . . . . . . . . . . . . . . . . . .
(1) Preparation
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
C . 3-Azaphenanthre
(2) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
I11 . 4-Azaphenanthrenes By J . A . Van Allan ........................ A . Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) From Glycerol (Skraup) .......................... B . Synthesis of the 4-Azaphenanthrene System . . . . . . . . . . . . . . . .
165 165 165 166 166 170 171 172 174
176 176 176 177 177 178 178 178 179 179 180 180 181 181 181 182 182 182 183 185 186 187 187 188 189 189 I90 191 191 192 206 206 209 209 21 1 211 211
216 216 217 217
Contents xv
(b) From a-0x0 Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(d) From ,9 .Diketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
( f ) From a Dialdehyde . . . . . . . . .
(h) From Acetoacetic Ester Type
(c) From a$-Unsaturated Aldehydes (Doebner-Miller) . . . .
(e) From Formyl Ketones ....................
(9) From a Formylamine . . . . . . . . . . . . . . . .
(1) From Acetoacetnaphthylide (Knorr) . . . . . . . . . . . . (2) From Ethyl 8-(2-Naphthy1amino)crotonate
(Conrad-Limpach) . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) From Ethyl Oxalacetate . . . . . . . . . . . . . . . . . . . . . . (4) From Ethyl Benzoylmalonate . . . . . . . . . . . . . . . . . . (5) From N-2-Naphthylbenzimidyl Chloride . . . . . . . . (6) From Ethoxymethylenemalonic Ester . . . . . . . . . .
(i) From 2-Naphthisatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( j ) From 1-Benzoyl-2-aminonaphthalene . . . . . . . . . . . . . . (k) From Epichlorohydrin . . . . . . . . . . . . [ 1) From Phenyl Isothiocyanate . . . . . . . . . . . . . . . . . . . . . . (m) From Naphthylthiourea . . . . . . . . . . . . . . . . . . . . . . . . . . (n) From Nitrosoacetamidophenylethylpyridine . . . . . . . . . . (0) From 1, 5-Diketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
thyl-2-naphthol . . . . . . . . . . . . . . . . . . . . C . Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
lfo-4-azaphenanthrenes . . . . . . . . . . . . . . (b) Amino-4-azaphenanthrenes . . . . . . . . (c) Hydroxy-4-azaphenanthrenes . . . . . . (d) Carboxy-4-azaphenanthrenes . . . . . .
D . Reactions of the Ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( 1 ) Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Halogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (4) Friedcl-Crafts . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(6) With Alkali Metals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E . Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(5) Cyanine Dyes . . . . . . .
(1 ) Physical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Chemical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Physiological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
F . Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
219 223 225 227 228 229 229 229
230 231 231 232 232 233 233 234 234 234 235 236 236 237 237 238 241 242 243 243 246 248 248 249 253 254 254 254 255 255 266
IV . 5.Azaphenanthrenes . By J . A . Van Allan . . . . . . . . . . . . . . . . . . . . . . 271 A . Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . 271 B . Methods of Synthesis . . . . . . . . . . . . . . . . . . . . . . . 2 72
(a) From Benzalaniline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272 (b) From Phenanthraquinone . . . . . . . . . . . . . . . . . . . . . . . . 272 (c) From Acyl-o-xenylamines (Morgan-Walls) . . . . . . . . . . 272 (d) From N-Methylcarbazole . . . . . . . . . . . . . . . . . . . . . . . . 279
( f ) From Fluorenone Oxime . . . . . . . . . . . . . . . . . . . . . . . . . . 281 (g) From Butadiene Derivatives . . . . . . . . . . . . . . . . . . . . . . 281 (h) From Cyclohexanone . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
(e) From Fluorylamines . . . . . . . . . . 280
XVI Contents
(i) From o-Halobenzaldehydes . ....................
(k) From Amidines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(m) From o-Aminobenzanilides . . . . . . . . . . . . . . . . .
(j) From Phenanthridones . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) From 2-hminobiphenyls and Benzotrichloride . . . . . . . .
C . Phenanthridinium Salts . . . . . . . . . . . . . . . . . . . . . D . Aminoalkylphenanthridines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E . Plant Alkaloids of the Phenanthridine Group F . Reactions of Phenanthridine Derivatives . . . . . . . . . . . . . . . . . . G . Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H . Direct Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
N-Oxides of Phenanthridine . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . .
I . Properties . . . . . . . . . . . . . . . . . . . J . Tables . . . . . . . . . . . . . . . .
References . . . . . . . . . . . .
V . Diazaphenanthrenes (except Phenanthrolines) . By John R . Thirtle . . A . 1, 2-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
B . 1.3-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (1) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Uses . . . . . . . . . .
C . 1. 4.Diazaphenanthren
(2) Nomenclature . . (3) Preparation . . . .
(1) Preparation and Properties . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Introduction . . . .
(a) From 1. 2.Dicarbonyl Compounds with 12-Naphthalene- diamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(b) From a-Keto Alcohols with 1. 2.Naphthalenediamine . . ( c ) From a-Halo Ketones with 1. 2.Naphthalenediamine . . (d) From 1-Nitroso-2-naphthol with Aldehydes and Xmines (e) From Azonaphthylamines and Ketones . . . . . . . . . . . . . . (f) From hzonaphthylamines and p-Oxoesters . (g) From Azonaphthylamines and B-Diketoncs . (h) Miscellaneous Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . .
( 1 ) From 1. 2.Naphthalenediaminc and Parabanic rlcid (21 From 1. 2.Naphthalenediamine and Phthalic An-
hydride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) From 1. 2-Naphthalenediamine and Selenonaph-
(4) From 1. 2.Xaphthoqoinone and Ethylenediamine . . (5) From 1.2-Naphthalenediamine and Isonitroso-
(6) From 1. 2.Naphthalenediamine and Biacetyl-
(7) From Dibenzo[a. j ] (8) From “Benzalloxa
thenequinone . . . . . . . . . . . . . . . .
acetophenone
monoxime . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(4) Substitution Reactions . . . . . . . . . . . . . . . . . . . . . . . . . (a) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(5) Replacement Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (6) Physical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . .
285 286 286 287 287 287 292 294 297 301 302 302 303 305 316
320 320 320 322 322 326 327 328 328 328 329
329 336 337 338 339 341 342 343 343
343
344 345
345
345 346 346 347 347 349 350
Contents XVII
(7) Uses .............................................. D . 1. 6.Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
E . 1, 8-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
F . 2, 3-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
G . 2, 4-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(2) 1Ceactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H . 3, 5-Diazaphcnanthrene . . . . . . . . . . . . . . . . . . . . .
(1) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2 ) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
I . 3, 6-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
J . 3, 8-Diazaphenanthrene . . . . . . . . ....................... ( 1 ) Preparation and Properties . . . . . . . . . . . . . . . . . . . . . . . . . .
K . 4. 5-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(2) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) Reduction of 2,P ’-Dinitrobiphenyl . . . . . . . . . . . . . . . . . . (b) From 2,2 ‘-Dihydrazinobiphenyl .................... (c) From 2,2 ‘-Diaminobiphenyl . . . . . . . . . . . . . . . . . . . . . .
(e) From Phenylhydrazones of o-Quinones (3) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
( 1 ) Preparation and Properties ..........................
(1) Preparation and Properties .......................... (2) Heactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
( 1 ) Preparation and Properties
(1) Preparation . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . .
(1 ) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
L . 5, 6-Diazaphenanthrene ..........................
(d) From Azobenzene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) Nitration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) Sulfonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (e) Metalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . .
VI . 1,lO-, 1,7-, and 4,7-Dianaphenanthrenes . By Bvuce Gvaham . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A . 1,l 0-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (1) History and Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Preparation (Ring Closures) ..........................
(a) Skraup-Type Reactions .......................... ( 1) Glycerol on o-Phenylenediamines (2) Glycerol on 8-Aminoquinolines . . . . . . . . . . . . . . . .
(4 ) From Ketals ................................
. . . . . . . . . . . . . .
(3) From a$-Unsaturated Aldehyde Diacetates ......
350 356 356 358 358 358 359 359 360 360 361 362 362 363 364 364 364 368 369 369 370 370 370 371 371 371 371 371 372 373 374 375 375 375 376 376 377 378 3 78 379 382
386 386 387 387 387 387 387 388 390 391
XVIII Contents
(5) From a.#? .Unsaturated Ketones (6) From 0x0 Alcohols .....................
. . . . . . . . . . . . . . . .
(b) Conrad-Limpach and Knorr Reactions . . . . . . . . . . . . . . (c) Doebner’s F’yruvic Acid Synthesis (From a-0x0 Acids) (d) From /?-Diketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (e) From Ethoxymethylenemalonic Ester . . . . . . . . . . . . . . ( f ) From /?-Chloroacid Chlorides . . . . . . . . . . . . . . . . . . . . . . (g) Other Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(3) Reactions of 1.1 0-Diazaphenanthrene (a) Salt Formation . . . . . . . . . . . . . (b) Hydration . . . . . . . . . . . . . . . (c) Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . .
(d) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (e) Nitration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (f) Other Reactions of th (g) Quaternization . . . . . . . . . . . . . . . . . (h) Complex Formation . . . . . . . . . . . . .
(4) Reactions of Substituted (5) Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) Analytical Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) Drying Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) Physiological Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
B . 1, 7-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (1) History and Nomenclature . . . (2) Preparation (Ring Closures) .
(a) Skraup-Type Reactions . . . ( 1 ) Glycerol on m-Phenylene . . . . . . . . . . . . . . (2) Glycerol on 5-Aminoquinolines . . . . . . . . . . . . . . . . (3) Glycerol on 7-Xminoquinolines . . . . . . . . . . . . . . . . (4) Glycerol on 5-Arylazoquinolines . . . . . . . . . . . . . . . . (5) Glycerol and Hydrochloric Acid on Nitroquinolines
(b) Conrad-Limpach Reaction . . . . . . . . . . . . . . (c) Doebner-Miller Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . (d) Doebner’s Pyruvic Acid Synthesis . . . . . . . . . . . . . . . . . . (e) From 8-Chloropropionyl Chloride . . . . . . . . . ( f ) Other Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(3) Reactions of 1,7-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . (a) Salt Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) Hydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) Quaternization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) Reduction . . . . . . . . . . . . . . . . . . . (e) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . (f) Nitration and Sulfonation . . . . . . . . . . . . . . . . . . . . . . . . (g) Halogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (h) Other Reactions . . . . . . . . . . . . . . . . . . . . . . .
(1) Benzilic Acid Rearrangement . . . . . . . . . . . . . (2) Chelation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(4) Reactions of Substituted 1, 7-Diazaphenanthrenes . . . . . . . .
(1) Replacement of 0x0 or Hydroxyl Groups by Halogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(2) Replacement of Hydroxyl Groups by Hydrogen . .
(a) Reactions of 0x0- and Hydroxy- 1, 7-diazaphenanthrenes
391 391 391 392 393 393 393 394 394 394 395 396 396 398 399 400 400 40 1 403 403 409 409 409 409 41 1 41 1 41 1 412 413 413 414 414 415 415 416 417 417 417 418 418 420 420 422 422 423 42 3 423 424 424
424 424
Contents XIX
(3) Replacement of Hydroxyl Groups by Amine Groups
(5) Cleavageof Ethers ............................ (b) Reactions of Carboxy-1.7-diazaphenanthrenes . . . . . .
(4) Etherification ................................
(1) Decarboxylation .............................. (2) Esterification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Hofmann Degradation ........................
. . . . . . . . . . (1) Replacement of Halogen by Amino or Substituted
(2) Replacement of Halogen by Alkoxy or Aryloxy Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(3) Halogen Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) Reactions of Amino.1. 7.diazaphenanthrenes . . . . . . . . (e) Other Reactions . . . . . .
(5) Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) Therapeutic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(6) Compounds Incorrectly Formulated as 1 ,7-Diazaphenan - threnes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
C . 4, 7-Diazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . (1) History and Nomenclature . . (2) Preparation (Ring Closures) . .
(c) Reactions of Halo- 1. 7.diazaphenanthrenes
Amino Groups ...................... . . . .
(b) Photosensitization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) Skraup-Type Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . ( 1 ) Glycerol on P-Phenylenediamine (or Its Nitro
Analogs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (2) Glycerol on 6-Aminoquinolines . . . . . . . . . . . . . . . . (3) Glycerol on 6-Nitroquinoline . . . . . . . . . . . . . . . . . . . . (4) Glycerol on -420 Compounds or Aminophenols . . . .
(b) Conrad-Limpach Reactions . . . . . . . . . . . . . . . . . . . . . . . . (c) Knorr Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) Doebner-Miller Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . (e) Doebner's Pyruvic Acid Synthesis . . . . . . . . . . . . . . . . . . (f) Price-Roberts Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . (g) From @-Chloropropionyl Chloride . . . . . . . . . . . . . . . . . . (h) Other Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(a) Salt Formation and Hydration . . . . . . . . . . . . . . . (3) Reactions of 4, 7-Diazaphe
(b) Quaternization . . . . .
(d) Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (e) Substitution (Electrophilic) . . . . . . . . . . . . . . . . . . . . . . . . ( f ) Benzilic Acid Rearrangement ......................
(4) Reactions of Substituted 4, 7-Diazaphenanthrenes . . . . . . . . (a) Reactions of 0x0- and Hydroxy-4, 7-diazaphenanthrenes
(1) Replacement of 0x0 or Hydroxyl by Halogen . . . . (2) Replacement of Hydroxyl Groups by Hydrogen . . (3) Etherification ................................
(b) Reactions of Carboxy-4, 7-diazaphenanthrenes . . . . . . . . (1) Decarboxylation ..............................
(4) Esterification ................................
(2) Esterification ................................
424 425 425 425 425 425 425 425
425
426 426 426 426 426 426 427
427 435 435 436 436
436 436 437 437 437 438 438 439 439 440 440 440 440 441 44 I 442 444 445 445 445 445 445 446 446 446 446 446
xx Contents
(c) Reactions of Halo-4,7-diazaphenanthrenes . . . . . . . . . . . . (1) Replacement of Halogen by Amino of Substituted
Amino Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( 2 ) Replacement of Halogen by Alkoxy or Aryloxy
Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) Reactions of Amino.4. 7.diazaphenanthrenes . . . . . . . . (e) Reduction of Nitro-4.7-diazaphenanthrenes . . . . . . . . . . ( f ) Oxidation of Side Chains . . . . . . . . . . . . . . . . . . . . . . . . . . (g) Other Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.................... . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
By John R . Thirtle . . . . . . . . . . . . . . . . A . 1,2, 3-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B . 1 2 , 4-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
VII . Other Polyazaphenanthrenes .
(2) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Isocyanate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) From 1-Phenylazo-2
(b) From “Naphthylphenylformazylbenzene’ ’ . . . . . . . . . . . . (c) From 1 -Phenylazo-2-naphthylcyanamide . . . . . . . . . . . . (d) From 1-Phenylazo-2-naphthylamine and Phosgene . . . . (e) From the Urethan of 1-Phenylazo-2-naphthylamine . . . . ( f ) From 2-Naphthylamine and Ethyl Azodiformate . . . . . . (g) FromEthyl l-Arylazo-2-naphthylaminoacetate . . . . . .
(3) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C . 1,2,1 0-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . D . 1,3, 4-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) From 2-Arylazo-1-naphthylamine and Phosgene . . . . . . (b) From 2-Arylazo- 1-naphthylamine and Phenyl Iso-
cyanate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) From I-Naphthylamine and Ethyl Azodiformate . . . . . . (d) From 1, 2-Naphthoquinone and Aminoguanidine . . . . . . (e) From 1-Nitroso-2-naphthol and Aminoguanidine . . . . . . ( f ) From 2-Phenylazo- 1-naphthylamine and Aldehydes . .
( 2 ) Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
(1) Preparation and Propcrties . . . . . . . . . . . . . . . . . . . . . . . . . . F . 1.4, 7-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . G . 1,5, 7-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H . 1,6. 7-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . I . 2,4, 6-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . J . 2.5.6-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . K . 4,5, 7-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . L . 1,2,3,4-Tetrazaphenanthrene .............................. M . 1,4,7,I 0-Tetrazaphenanthrene ............................ N . 2,3,4, 6-Tetrazaphenanthrene .............................. 0 . 2,3,5, 6-Tetrazaphenanthrene .............................. P . 1,3.5,6,8,1O-Hexazaphenanthrene ........................
References ............................................
hthylamine and Phenyl
E . 1,3, 7-Triazaphenanthrene . . . . . . . . . . . . . . . . . . . . . . . . . . . .
446
446
447 447 447 447 448 448 454
457 457 458 458 458
458 459 459 449 460 460 461 463 464 465 465 465
465 466 467 467 468 468 469 470 470 472 474 474 475 476 477 478 479 480 481 482 482
Contents XXI
WtI. Azabemonaphthenes . By James H . Richmond . . . . . . . . . . . . . . . . . . 484 1 . Historical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484 2 . Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 3.Monoazabenzonaphthenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
A . 1H. 1-Azabenzonaphthene ................................ 485 B . 1H. 2.Azabenzonaphthene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
(1) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 (a) Electrolytic Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 (b) Ring Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 (c) Chemical Reduction .............................. 490 (d) Beschke Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
(2) Naphthalimidines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 (3) Naphthalimides .................................... 495
(a) Preparation ...................................... 495 (b) Halonaphthalimides .............................. 502 (c) Aminonaphthalimides ............................ 503
Chemical Properties ............................ 505 Uses ........................................ 505
(d) 2-Aminonaphthalirnides .......................... 505 Nomenclature ................................ 512
(e) Hydroxynaphthalimides . . . . . . . . . . . . . . . . . . . . . . . . . . 512 (1) Phenols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512 (2) Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
(f) 2-Hydroxynaphthalimides . . . . . . . . . . . . . . . . . . . . . . . . 512 (g) Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514 (h) Mercury Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
(a) Ring Cleavage . . . . . . . . . . . . . . . . . . . . . . . (b) Dehydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515 (c) Dehydrogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
(5) Uses of Naphthalimides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 516 4 . Polyazabenzonaphthenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517
A . 3H, 1. 2-Diazabenzonaphthene . . . . . . . . . . . . . . . . . . . . . . . . . 517 B . Perimidine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 518
(1) Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 520 (2) Properties and Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526
(a) Dehydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 527 (3) Products of Indeterminate Structure . . . . . . . . . . . . . . . . . . 528 (4) Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529 (5) Reduced Perimidines; 2,3-Dihyclr o- IH, 1.3-diazabenzo-
naphthenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529 (a) 2.2-Disubstituted 2,3-Dihydroperimidines . . . . . . . . . . . . 534
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535 (b) Perimidones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538 Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540
(c) 2-Imidoperimidine .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540 (d) Thioperimidones; 2-Thioperimidines . . . . . . . . . . . . . . . . 541
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542 Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
C . lH, 1,2, 3-Triazabenzonaphthene . . . . . . . . . . . . . . . . . . . . . . . . . . 543 Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544 References ............................................ 546
(4) Reactions of Naphthalimides . . . . . . . . . . . . .
XXII Contents
IX . The Ultraviolet Absorption Spectra of Polycyclic Heterocyclic Aromatic Compounds . By G . M . Badger . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
1 . Aromatic Hydrocarbons and Azahydrocarbons . . . . . . . . . . . . . . . . 551 2 . The Color of Aromatic Azahydrocarbons . . . . . . . . . . . . . . . . . . . . . . 558 3 . Absorption Spectra of Diazines and Related Compounds . . . . . . . . 559 4 . The Effect of Substituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 566
Naphthalimides: Addendum . 567 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571
By C . F . H . Allen ....................
Introduction
BY C. V. WILSON
The heterocyclic compounds described in this volume are azalogs of anthracene (I), phenanthrene (11) and benzonaphthene (111). Though
many of the derivatives of these ring systems can be prepared by the usual substitution or replacement reactions, the basic structures are the result of certain well-known cyclization procedures, including the Skraup, Doebner, Doebner-Miller, Combes, Conrad-Limpach, Pfitzin- ger, and Knorr carbostyril syntheses. These ring closures may lead to either angular (IV) or linear (V) compounds. The Skraup, Doebner-
Miller, and Conrad-Limpach syntheses are commonly associated with angular cyclization. Generally, they must be modified to give the linear product, though occasionally both isomers result. Conversely, the Combes synthesis, which normally leads to the linear isomer, can be modified to produce the angular product.
The various cyclization procedures used in the syntheses of these heterocycles may be divided into two general classes; (I) those in which cyclization is effected by removal of HX (generally H,O) from ortho-
1
2 Introduction
disubstituted naphthalene derivatives containing a nitrogen atom in at least one of the substituent groups, as indicated in types VIa, b, and c;
(2) those in which the naphthalene nucleus is only monosubstituted and cyclization involves the removal of a hydrogen atom from an ortho position, usually as water or hydrogen (VIIa and b). I t is obvious that the former type of cyclization is unambiguous and that either
(VIIa) (VIIb)
angular or linear heterocycles can be obtained by the proper choice of starting material. In the latter case, however, it is just as clear that the cyclization can proceed in two ways to give either a linear or an angular product.
The Pfitzinger reaction is an example of the first type (see p. 28);
COOH
obviously it can be used to produce the angular isomer by starting with the isomeric naphthisatin1p2 (see pp. 177 and 233). Another example involves the use of methazonic acid (see p. 30) ; this substance
Introduction 3
reacts with 2-amino-3-naphthoic acid, and the resulting product can be cyclized with sodium acetate and acetic anhydride. It should be
N= CHCH,NO, - CHCH,NO,
N-OH /I COOH
possible to obtain the angular isomer by the proper choice of starting material. In these examples the cyclization can proceed in one way only, and there can be little doubt as to the structure of the product.
The second type of reaction, including such syntheses as the Skraup, Doebner-Miller, Combes, Knorr, and Conrad-Limpach, can proceed in two different ways to give either an angular or a linear product. Thus, a problem of structure arises; while the nature of the product or products obtained has been established in many cases, instances are still recorded in which the structure is in doubt.The use of ultraviolet absorption spectra is a valuable aid in the study of such problem^.^^
In general, the Skraup, Doebner-Miller, Knorr, and Conrad- Limpach syntheses, applied to 2-naphthylamine, lead predominantly to angular cyclization. A small amount of the linear product may be formed simultaneously. However, three of these syntheses (Skraup, p. 24; Knorr, p. 27; Conrad-Limpach, p. 26) will yield a linear product if the 1-position of the 2-naphthylamine ring is blocked by a chlorine or a methyl group (VIII). Some of the angular derivative may also be formed by the ejection of the blocking group.5-* The l-aza- anthracene (IX) formed in these reactions is not isomeric with the normally formed 4-azaphenanthrene because it contains a substituent in the 9-position. Nevertheless, the syntheses that commonly produce angular derivatives lead in these cases to linear compounds.
4 Introduction
The Doebner synthesis (an amine, aldehyde, and pyruvic acid) normally leads to an angular product, but when the 1-position is blocked in an attempt to effect linear cyclization, as X, a totally different type of reaction occurs, a pyrrolidine (XI) being formed.5
R'
(XI (XI)
A reaction somewhat similar to this occurs when one attempts to cyclize 2-(2-acetamido- 1 -hydroxyethyl)naphthalene (XII). Neither an
CH,-N
CHOHCHZNHCOCH, /-.,,++ L H C--CH3 " I ,9 I '0' \ /
(XW (XIII)
azaphenanthrene nor an azaanthracene, but a 5-B-naphthyloxazoline (XIII) is formed.1°
The Combes synthesis, which normally gives the linear isomer, can be modified to produce the angular product. The change is so marked that it bears little resemblance to the original Combes synthesis other than the use of 2-naphthylamine and an a,&dicarbonyl compound. Concentrated sulfuric acid or hydrogen fluoride yield the abnormal, linear product,*. l1*l2 while hydrochloric acid, ethyl alcohol, and zinc chloride give the normal angular i ~ o m e r . ~ The blocking procedure, employed successfully in the Skraup synthesis, has not been useful in this case. The Schiff base from 2-amino-3-methylnaphthalene, for example, is hydrolyzed into its components under the conditions of the reaction before cyclization to the 4-azaphenanthrene derivative can be effected?.l3 It is possible that under nonhydrolytic conditions (e.g., by heating in Dowtherm) this reaction may take place.
I t is of interest that the Skraup reaction and each of the variations of the Doebner-Miller reaction has a Combes reaction as its counterpart. The former type proceeds by the primary addition of the amine to a,,+unsaturated ketones (or aldehydes), the latter by the formation of
Introduction 5
a Schiff base from 1,3-diketones (or aldehydes). In the accompanying table the relationship of the two types of active groups that react with 2-naphthylamine is shown. All of these reactions, except that of
SKrau f i or Doebner-Miller Combes
Starting product Reactive intermediate
CH,OHCHOHCH,OH CH,= CHCHO OHCCH,CHO
CH,CHO CH,CH = CHCHO CH,COCH,CHO
CH,CHO + (CH3),C0 CH,CH = CHCOCH, CH,COCH,COCH,
CH,0CH,CH,COCH3 CH,= CHCOCH, OHCCH,COCH,
malonic dialdehyde with 2-naphthylamine, have been reported. I t is possible that this aldehyde may produce 1-azaanthracene, which has been difficult to procure by other procedures.
A comparison of the primary product from 2-naphthylamine and an a,,!?-unsaturated ketone with that from the corresponding diketone points up the difference in structure that is presumably the cause for angular cyclization in one case and linear in the other. The Schiff base (XIV) gives the linear product while its reduced form (XV) gives the
angular. A possible mechanism for the anomolous, linear ring closure is discussed on p. 10.
In addition to the blocking effect and the influence of substituents in the side chain in determining the course of the reaction, there is another feature that has an effect. This is concerned with the type of ring structure that is fused to the aromatic amine. In the case of 2-naphtliylamine, of course, it is a benzene ring. If the latter is reduced, i e . , as in 6-aminotetralin, application of the Skraup synthesis leads to a mixture of angular and linear products with the latter predomi- nating.14 Since 2-naphthylamine gives only an angular product with the Skraup synthesis, it is apparent that the disposition of electrons is
6 Introduction
modified in the reduced form in such a way that linear cyclization is favored.
This effect is again demonstrated in the application of the Bischler- Napieralski reaction to N4P-6- te tralyle t hyl) phen ylace tamide (XVII) .
Here, cyclization is exclusively linear.I6 On the other hand, it:is probable that only the angular product (XVIII) is formed from 2-@benzamido- ethyljnaphthalene (XIX),15 analogous to the synthesis of 1,2,3,4-tetra-
( X W (XV 111)
hydro-2-azaphenanthrene (XX) from 2-(#haminoethyl)naphthalene (XXI) and formaldehyde.ls
(XXI) (XX)
It is obvious, therefore, that the type of product obtained cannot be predicted solely from the type of reaction used to effect the cycliza- tion. Consideration must be given to the atoms carried in the molecule, especially with respect to their activating or deactivating influence on the 1- or 3-position.
One other problem in connection with these two types of syntheses is worthy of attention. This arises from the fact that the cyclization of a Schiff base (XXII) to a substituted 1-azaanthracene requires no
\/\/ CH,
(XXII) (XX I I I)